POS0227 SERUM EXTRACELLULAR MATRIX BIOMARKERS IDENTIFY RESPONSE TO GUSELKUMAB IN PSORIATIC ARTHRITIS: POST-HOC ANALYSIS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY THROUGH 2 YEARS
Authors: S. Holm Nielsen, A. C. Bay-Jensen, P. Frederiksen, M. Karsdal, M. Shawi, S. D. Chakravarty, A. Kollmeier, W. Chen, S. Gao
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic arthritis (PsA) is a progressive, joint-degenerative inflammatory disease with cartilage destruction, bone erosion and growth, and synovitis. Extracellular matrix (ECM) remodeling is also observed in skin lesions in patients with PsA. Guselkumab (GUS), an interleukin-23p19-subunit monoclonal antibody, demonstrated robust efficacy compared with placebo in patients with active PsA in two Phase 3 studies, DISCOVER-1 and DISCOVER-2.<sup>[1,2]</sup> GUS also reduced serum ECM biomarkers shown to be elevated in patients with PsA.<sup>[3]</sup> <h3>Objectives</h3> To identify treatment responders among PsA patients receiving GUS, using serum biomarkers of collagen formation, degradation, and vimentin degradation. <h3>Methods</h3> Available baseline serum ECM biomarker data from patients who consented to participate in the 2-year DISCOVER-2 trial (NCT0315828) were included in the post hoc analysis. Biomarkers of collagen formation (PRO-C2, PRO-C3, PRO-C4, and PRO-C6), degradation (C1M, C2M, and C6M), and citrullinated and degraded vimentin were measured by immunoassays. Baseline ECM biomarker levels from all available patients were log-transformed and standardized by mean centering and scaling by the standard deviation prior to K-means clustering. In GUS-treated patients, between-cluster comparisons for major demographic and clinical parameters were performed using Mann-Whitney or chi-squared tests. Relationships between observed clinical response (ACR20, ACR50, PASI100) at Week (W)24, W52, and W100 and baseline levels of biomarkers were investigated. Analysis of PASI response was performed in patients with baseline body surface area (BSA) ≥3% and Investigator's Global Assessment (IGA) of psoriasis score ≥2. <h3>Results</h3> Two distinct clusters were identified using baseline serum ECM biomarkers from all patients (Figure 1). Patients in Cluster 1 generally had lower levels of ECM biomarkers than patients in Cluster 2. In GUS-treated patients, those in Cluster 2 had a higher (all p&lt;0.05) baseline PASI score (median 7.3 vs 5.1), swollen joint count (12.0 vs 10.0), C-reactive protein (2.0 vs 1.0 mg/dL), and PsA-modified vdH-S score (26.5 vs 13.0). Relative to patients in Cluster 1, GUS-treated patients in Cluster 2 showed a greater ACR20 response rate at W24 (72% vs 57%, p=0.039) and W52 (80% vs 66%, p=0.037) and a greater ACR50 response rate at W100 (64% vs 47%, p=0.031), indicating patients with high levels of these biomarkers were more likely to achieve an ACR response. For patients with at least mild skin disease at baseline (BSA≥3% and IGA≥2), those in Cluster 1 demonstrated a higher PASI100 response rate at W100 than patients in Cluster 2 (71% vs 54%, p=0.046). <h3>Conclusion</h3> Patients with higher levels of baseline ECM biomarkers (Cluster 2) that correspond with greater peripheral joint inflammation demonstrated higher ACR20 and ACR50 response rates when treated with GUS, while patients with lower levels of these ECM biomarkers (Cluster 1) demonstrated higher rates of complete skin clearance (PASI100). These findings may provide a step towards patient stratification and precision medicine for guiding the use of biologic immunomodulatory treatments in patients with PsA. <h3>References</h3> [1]Deodhar, A et al. <i>Lancet.</i> 2020;395:1115–25. [2]Mease, PJ et al. <i>Lancet.</i> 2020;395:1126–36. [3]Schett, G et al. <i>Rheumatol Ther.</i> 2022;1–14. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Signe Holm Nielsen Employee of: and shareholders of Nordic Bioscience, Anne-Christine Bay-Jensen Employee of: and shareholders of Nordic Bioscience, Peder Frederiksen Employee of: and shareholders of Nordic Bioscience, Morten Karsdal Employee of: and shareholders of Nordic Bioscience, May Shawi Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson and may own stock or stock options in Johnson &amp; Johnson, Soumya D Chakravarty Employee of: Employee of Janssen Scientific Affairs, LLC and may own stock or stock options in Johnson &amp; Johnson, Alexa Kollmeier Employee of: Janssen Research &amp; Development, LLC and may own stock or stock options in Johnson &amp; Johnson, Warner Chen Employee of: Janssen Research &amp; Development, LLC and may own stock or stock options in Johnson &amp; Johnson, Sheng Gao Employee of: Janssen Research &amp; Development, LLC and may own stock or stock options in Johnson &amp; Johnson.